Identification and Treatment Of Unstable Plaque with OCT

描述(由申请者提供)：该计划是NIH R01 EB002638(前NIH R01 HL63953)的竞争性延续，名为“提高光学相干断层扫描对易损斑块评估的诊断潜力”。这项工作的长期目标是开发一种新的高分辨率血管内成像方法，以克服目前心脏诊断的局限性，主要是识别可能导致急性冠状动脉综合征(即心肌梗死或不稳定型心绞痛)的冠状动脉斑块。大多数急性冠脉综合征(ACS)是由冠状动脉中的小斑块而不是大斑块破裂引起的。这些脆弱的斑块是最典型的薄帽纤维动脉粥样硬化瘤(TCFA)，它包含相对大量的复杂坏死核心，具有高浓度的脂质和出血，以及覆盖在上面的薄薄的胶原耗尽的内膜帽。当这些斑块破裂时，它们会将血栓物质释放到血液中，形成血栓，血管经常闭塞。这些小斑块超出了目前任何可用的成像设备的检测极限。光学相干层析成像(OCT)是一种新的高分辨率成像方法，在评价不稳定斑块方面显示出巨大的潜力。部分通过NIH RO1 HL55686和R01 HL63953/EB002638产生的初步数据强烈表明OCT用于易损斑块评估的可行性。10微米的分辨率使动脉内的微结构得到了前所未有的定义。随着OCT现在被引入用于活体人体成像，允许识别一些TCFA，一个重要的问题出现了。大多数急性冠脉综合征是TCFA的结果，但大多数TCFA不会导致急性冠脉综合征。虽然OCT可以识别内膜直径小于70微米的斑块，这比其他成像方法有了很大的进步，但OCT需要进一步对这些斑块进行风险分层，而不是TCFA的识别，这是目前的技术水平。如果要在21世纪继续在这一领域取得进展，就必须把重点放在高危患者身上，这些患者的病变容易发生血栓，以及导致斑块在准确的位置和时间破裂的触发机制。这一建议的假设是，OCT技术可以通过开发辅助技术来改进薄层动脉粥样硬化的风险分层，识别那些导致急性冠状动脉综合征的患者。随着技术的进步，对体外人类冠状动脉的评估，体外红细胞注射(出血性)兔动脉斑块(目前产生与人类TCFA最相似的斑块的大型动物模型)的成像，兔动脉粥样硬化斑块的体内成像，以及对治疗药物诱导的体内变化的监测，这一假说将得到验证。此外，我们将同时尝试通过诱导血管生成来进一步改进兔出血性斑块模型，血管生成可能最终是许多斑块破裂的触发因素。

DESCRIPTION (provided by applicant): This program is a competing continuation of NIH R01 EB002638 (formerly NIH R01 HL63953) "Improving the Diagnostic Potential of Optical Coherence Tomography for Vulnerable Plaque Assessment". The long- term objective of this work is to develop a new method of high resolution intravascular imaging to overcome current limitations in cardiac diagnostics, principally the identification of coronary plaques likely to lead to acute coronary syndromes (i.e. myocardial infarction or unstable angina). Most acute coronary syndromes (ACS) result from the rupture of small rather than large plaques in the coronary arteries. These vulnerable plaques are most typically thin cap fibroatheromas (TCFA) that contain a relatively large amount of complex necrotic core with a high concentration of lipid and hemorrhage, and an overlying thin collagen-depleted, intimal cap. When these plaques rupture, they release thrombogenic material into the blood, a clot forms, and the vessel frequently occludes. These small plaques are beyond the detection limit of any currently available imaging modalities. Optical coherence tomography (OCT), a new method of high resolution imaging, has demonstrated great potential for the assessment of unstable plaques. Preliminary data, generated in part through NIH RO1 HL55686 and R01 HL63953/ EB002638, has strongly suggested a feasibility of OCT for vulnerable plaque assessment. The 10 urn resolution allowed unprecedented definition of microstructure within arteries. As OCT is now being introduced for in vivo human imaging, allowing the identification of some TCFA, an important concern arises. Most ACS result from TCFA, but most TCFA do not lead to ACS. While OCT can identify plaques with intimal caps less than 70 urn, a substantial advance over other imaging modalities, a need exists for OCT to further risk stratify these plaques beyond the identification of TCFA, which is the current state of the art. If progress inthe field is to continue in the 21 st century, one must focus on high-risk patients with lesions that are vulnerable to thrombosis together with the triggering mechanisms that cause plaques to rupture at a precise location and time. The hypothesis of this proposal is that OCT technology can be advanced through the development of adjuvant technologies to improve risk stratification of thin cap atheromas, identifying those which lead to acute coronary syndromes. The hypothesis will be tested with advancements of the technology, assessment of in vitro human coronary arteries, imaging of in vitro RBC injected (hemorrhagic) atherosclerotic rabbit plaque (the current large animal model producing plaques most closely resembling human TCFA), in vivo imaging of rabbt atherosclerotic plaque, and monitoring in vivo changes induced with therapeutics. In addition, we will in parallel attempt to further improve the rabbit hemorrhagic plaque model by inducing angiogenesis, the factor which may ultimately be the trigger of many plaque ruptures.